All right. I'd like to welcome everyone to day one, company one of the Piper Sandler Healthcare Conference. I'd like to welcome Compass Therapeutics, their CEO, Tom Schuetz. Welcome, Tom.
Thanks, Biren. Thanks for having us at the conference. Really appreciate it.
I was looking at your stock price year to date, up 290%. I mean, that's quite impressive compared to XBI of 30%. The company's clearly doing something right. Can you tell us, maybe we start off with the two clinical stage programs, and if you could maybe provide us an overview of both programs, targets, indications, and then we can dig in a little bit more.
Sure. Yeah, I think to your first point, I think it might be related to our high-quality analyst coverage. Compass Therapeutics, we're located in Boston. We're a monoclonal antibody discovery and development company in oncology. We actually have three drugs in the clinic, two bispecific antibodies, and one monoclonal antibody, and a third bispecific antibody going to enter the clinic early in the coming year. Our most advanced program is a DLL4 x VEGF-A bispecific antibody. That drug is called Tovecimig. That is currently in a randomized trial in patients with advanced biliary tract cancer. Earlier this year, we announced that we hit the primary endpoint in a randomized trial of overall response rate, more than tripling the response rate seen in the control arm. To my knowledge, we have one of the highest response rates ever seen in patients with advanced biliary tract cancer treated in the second-line setting.
In addition, which we'll get into this, I'm sure, there was a substantial difference in the disease control rate as well, suggesting that we could see an important difference in progression-free survival as well. We'll come back to that point in a minute. Our second program that is currently in a clinical trial is a drug called 8371. That is a novel, potentially first-in-class PD-1 x PD-L1 bispecific antibody that came out of a screen for synergy with PD-1 blockade using a technology that our scientists at Compass developed. Our scientists did a screen for synergy with PD-1 blockade and made an important discovery that PD-L1 blockade is the best combination partner for PD-1 blockade in a bispecific antibody. That drug has recently completed a dose escalation phase I study. Fascinatingly, we saw no dose-limiting toxicities in that study.
More importantly, 15 patients treated in the post-checkpoint setting, we already have three responses. We have three confirmed responses now, including a patient with non-small cell lung cancer, triple-negative breast cancer, and a third indication we've not yet disclosed. The patient with triple-negative breast cancer is extremely important. This patient relapsed while receiving Adjuvant KEYTRUDA. Technically speaking, this patient is actually refractory. Then received TRODELVY, followed by two additional chemotherapy regimens. Started the study with approximately 9 cm of tumor burden, and that is now down to approximately 5 mm. Greater than a 90% decline. The patient is now durable, continuing on therapy. Potentially, this patient could convert to a complete response, which would be absolutely amazing. I just want to make one final point about 8371.
I know I'm repeating myself, but all of the patients were treated in the post-checkpoint inhibitor setting, and we already have three responses in the first 15 patients treated. I believe, of course, I'm biased, we have the best phase I data of any checkpoint inhibitor ever. Drugs like KEYTRUDA, OPDIVO, TECENTRIQ, those were all tested in the checkpoint naive patient population. This is a little bit of a subtle point, but I believe this is extremely important that we're seeing monotherapy responses in the post-checkpoint patient population.
That's great. I mean, both seem like very exciting programs with a lot of potential. I guess maybe if we could start with Tovecimig, COMPANION-002 trial, it's phase II/III , pivotal study. As you mentioned, you've reported the primary endpoint, achieved that on overall response rate versus paclitaxel alone. PFS, OS endpoints are expected by the end of Q1. Can you tell us how we should look at the read-through from overall response rates to PFS and OS and the confidence in the PFS and OS endpoints? I think also you had disclosed that at eight weeks, there were a significantly greater number of patients that progressed in the PAC arm versus the Tovecimig arm. Maybe can you talk about the read-throughs from that data point as well?
Sure. We reported the best overall response rate data in April of this year. Of course, best overall response rate can include many different things. It can, of course, include complete responses, and we had a complete response as adjudicated by blinded independent central review, an extremely unusual finding in advanced biliary tract cancer. Partial response, stable disease, but progressive disease can also be your "best overall response." Thank you. If PD is your best overall response, what that means is by definition, it had to occur at the first scan time point, which was at week eight. If you had stable disease at week eight, you would be in the SD category. If PD was your best overall response, what that means is it had to occur at week eight. In the combination arm, we only had 16% PD.
In the combination arm, as you mentioned, we had 42%. 100 minus those numbers is a maximum of 58% progression-free survival maximum at week eight, 84% in the combination arm. The progression-free survival curves are probably already significantly diverging. We're quite confident that we'll hit the PFS endpoint. I think one of the things you asked an important question about read-through, right? I think one of the things to keep in mind with the read-through from the response rate to the PFS and OS endpoints is the waterfall plots. The waterfall plots from the study are fundamentally different. In the combination arm, the majority of patients had decreases in their linear tumor burden, which I alluded to earlier with the disease control rate. The disease control rate was close to double in the combination arm as compared with the control arm.
We believe that will read through directly to PFS. As you mentioned, both PFS and OS analyses are triggered by OS events. We reported in August, and then we reiterated in November with our Q2 and Q3 earnings releases, respectively, that we're seeing fewer deaths in the study than we initially projected. Because of that, we've recently updated at 18 months median follow-up. When we still had not hit the number of total events, we were well above where you'd be expected based on historical data in this disease. We're enthusiastic about the OS endpoint, and as you mentioned, looking forward to reporting those data toward the end of Q1 of the coming year.
You mentioned that the OS event rate has been slower to accrue. This is a two-to-one randomized design. Clearly, with 80% events that are required for the study to unblind, you would need patients in the active arm to have an event. Is that a fair characterization? In your view, what do you think are the reasons why the events have been slow to accrue?
Sure. A two-part question there. The first part of your question is yes. We need to see 80% pooled OS events in order to trigger the analyses of PFS and OS. The second part of your question, of course, is very important, but also, of course, very complicated. Whenever you see something like this, you wonder whether or not the control arm is doing something that you did not anticipate. Do we have any evidence to support that? Probably not, because in our best overall response rate analysis, the response rate in the control arm was only 5.3%. Paclitaxel is not doing something that we did not expect. The three-drug combination FOLFOX in a randomized trial had a response rate of 4.9%. So 4.9%, 5.3%, those are the same numbers. We are not seeing it there.
In terms of the incidence of progressive disease, with 42% progression at week eight, the median PFS in the control arm is probably going to be something like 2 months-2.5 months. It's going to be in that range. I don't know what it's going to be, but based on our overall response rate data, it suggests that it's in that range. The control arm is not doing something unanticipated. I know for sure that we are not missing data. We've had extremely low numbers of patients lost to follow-up in this study. I think our clinical operations group at the company is just doing a phenomenal job here. We've only lost something like 5% of patients to follow-up, which is just a staggering low number for this study.
I know today that every patient, except for one single patient that is known to be alive today, was known to be alive in either October or November. We are very up to date on data collection, which then leaves the third possibility that we are seeing a drug effect, which is, of course, what we believe. We believe that what we are seeing is fewer patients have died, more patients are alive for a longer period of time because Tovecimig is affecting overall survival. That is what we believe.
In the paclitaxel control arm, there is an option for those patients to crossover to receive Tovecimig. Can you talk a little bit about the percentage of patients that have crossed over and have received Tovecimig in the trial? The first question is, how are you going to account for those patients that crossover onto Tovecimig in your OS analysis?
Okay. The first part of your question, we know that about half the patients, approximately half the patients in the control arm crossed over to receive active drug, which also could be contributing perhaps to the fewer number of OS events that we're seeing. We are accounting for crossover using a statistical technique called the Rank Preserving Structural Failure Time, RPSFT. This is a statistical analysis that adjusts the Kaplan-Meier overall survival curves for crossover. This statistical technique was actually used in biliary tract cancer in a randomized trial that led to FDA approval in the study called ClarIDHy, C-l-a-r-I-D-H-y, ClarIDHy, which was a study of the IDH1 inhibitor Tibsovo versus placebo. That also allowed a crossover in that study a little bit more than 1/2, maybe closer to 2/3 of patients actually crossed over, and they used the RPSFT to analyze their overall survival data.
It is my understanding—by the way, I don't know if this is true or not—but it is my understanding from talking to folks who were at Agios at the time that the RPSFT was recommended to Agios by the FDA. That is what I was told. I assume that is true. With the RPSFT, the adjusted hazard ratio for OS in the ClarIDHy study was 0.49x, and that got that drug labeled in second-line BTC. You could not have a more perfect regulatory precedent for us.
This is going to be your primary OS analysis is going to be on the Rank Preserving Structural Failure Time analysis.
Yes.
Can you talk a little bit about the stats hierarchy after OR? What's the next endpoint that you're going to look at? Is it PFS or is it OS?
PFS. The stats hierarchy is important because we're using a technique called hierarchical testing to control for alpha spend. There are a couple of ways to do that. One commonly used way is to "split" the alpha, but hierarchical testing has been shown to control alpha spending better than alpha splitting. The way that hierarchical testing works is you do the primary endpoint analysis, if that's positive, which it was, with a p-value of 0.031. All of the alpha error then rolls over to the next analysis, which is PFS. If PFS is positive, a full 0.05 alpha rolls over to the OS analysis, then to the DOR analysis.
Got it. How do you think you talked about ClarIDHy and how FDA looked at the Rank Preserving Structural Failure model? Have you had discussions with FDA or other regulatory experts on the acceptance of this model, given the draft guidance on the OS endpoint that was issued by FDA earlier this year?
In that draft guidance, I think it's fairly clear in that guidance that in indications of tremendous unmet need, that crossover is acceptable to FDA. In second-line biliary tract cancer in the United States, outside of patients who have tumors with actionable mutations, which unfortunately is a small fraction of the patient population, there is literally no labeled therapy in the United States. It's an unimaginable unmet need with no labeled therapy. In those scenarios, crossover designs are acceptable. The RPSFT was in the protocol from the beginning, and our statistical analysis plan was submitted well over a year ago, just after the study was fully enrolled, way, way ahead of time. FDA had no comments on that.
Great. The study's on track for completion in Q1 in terms of the PFS/OS readout. After that readout, what are next steps on filing the BLA? Should we expect that to occur, I guess, in the second half of the year?
I think the next step after the PFS and OS readouts would be to complete the full analysis of every endpoint in the study and then have a meaningful interaction with the FDA. Presumably, that interaction would occur in Q2, which would put us in a position, if that interaction went well, to submit a license application in the second half of the year. We have fast-track designation, so we would certainly get a priority review, which should put our PDUFA date inside the first half of 2027. We could potentially be within, call it, 18 months of launching this drug in the United States.
That's great. What's the market potential in second-line biliary tract cancer in the U.S.?
Sure. Biliary tract cancer is much more common than you might think. About 25,000 patients annually are diagnosed with biliary tract cancer. There was a recent JAMA Oncology article indicating that the incidence of biliary tract cancer is increasing. Over the next decade, it is projected to become one of the most common malignancies in the country. So 25,000 patients annually. Some of those patients are eligible for surgery. Unfortunately, only about 10% of patients-ish get surgery. About half those patients relapse. We did some third-party market research earlier this year that was commissioned by—we commissioned a well-known firm to do that market research, 70 physician-payer interviews and surveys. Based on all of that work, which is a very large project, we believe about 15,000 patients annually in the United States alone would be eligible for this therapy.
It is about three times larger than the platinum-resistant ovarian cancer market. If you think about the rest of the world, Japan, which has a smaller population, of course, than the U.S., but the incidence of BTC in Japan is higher. The total number of patients in Japan is probably close to the total number of patients in the U.S.. The EU, of course, is just about twice the size of the United States. There are probably well over 100,000 patients diagnosed annually just between the EU, Japan, and U.S. It is a very, very large market.
How does the company think about the ex-U.S. opportunity? Would you commercialize it yourself, or would you potentially seek a partner?
I think in the United States, we're preparing to commercialize this drug ourselves. I think biliary tract cancer is an indication where patients are mostly seen at academic centers, so a small targeted sales and marketing force. I think we can launch this drug ourselves, and we are preparing to do so. We'll have more to say about that in terms of our commercial infrastructure in the beginning of the coming year. I think one of our corporate goals for 2026 will be to initiate regulatory interactions in Japan and the EU. Your specific question, we have said publicly that we're having some conversations with potential strategic partners about ex-U.S. geographies. Of course, we'll do what's in the best interest of our shareholders. We'll see.
We have a few minutes. I do want to touch on 8371.
Okay.
There are five dose cohorts that you evaluated in the dose escalation. In the next phase of the study, I believe you're going to evaluate two of those cohorts. Have you decided which two doses you're going to evaluate for the next phase of the study?
Yes. Because we've seen this truly, again, in my view, remarkable efficacy signal in phase I dose escalation, we now are going to move to cohort expansions. We are going to enroll patients with non-small cell lung cancer and triple-negative breast cancer into two cohorts of 28 patients each, so a total of 56 patients. Within those 28 patients, within each indication, they will be randomized to one of two doses, 3 mg per kg or 10 mg per kg. We have decided on the two doses just based on what we've seen early on and enrolling those patients to do some small Project Optimus work in terms of dose finding, identify a phase II dose, confirm the efficacy signal we've seen in dose escalation. I think non-small cell lung cancer, of course, is a more complicated indication for sure, but triple-negative breast cancer is not.
Post-Trodelvy, if we're seeing responses in that patient population, I'm quite confident that that would be a single-arm response rate study to approval. In the first half of next year, if we confirm the efficacy signal in patients with triple-negative breast cancer, we're going to move directly to a potential approval study next year. The third indication, and by the way, we enrolled patients with one of five tumor types into the study. In addition to non-small cell lung cancer and triple-negative breast cancer, we enrolled patients with melanoma, head and neck cancer, and Hodgkin's lymphoma. We've had a third response at the highest dose level in one of those other three indications, which we have not yet disclosed, waiting for some more data from that patient.
That indication is very, very interesting, and we're now working with some KOLs on potentially going straight to a phase II study that also, again, in the post-ADC, post-PD-1 patient population, would be a potential approval study. I think 2026 is going to be an incredibly exciting year for 8371, with moving to two potential approval trials with that drug next year. That's a drug we're incredibly excited about. I think if we have discovered the first next-generation checkpoint inhibitor, we'll be off to the races.
That's great. I mean, a lot of exciting updates over the next 12 months. You also have a third program that you're potentially moving into the clinic with the PD-1/VEGF, and I think the IND is expected to be filed soon. How does that fit in, given the excitement of the first two programs? Do you plan to carry that on yourselves, or would you potentially partner it at some point?
Sure. Our fourth program, as you mentioned, a drug we call 10726, a PD-1/VEGF bispecific antibody. This is now a new class of drug. Many companies are now working on this class of drugs, and we have a very novel drug candidate. We presented some data last month at SITC, suggesting that in certain preclinical models, our drug is superior to Ivonescimab. You are correct. IND filing followed by phase I initiation in the first half of next year. Our phase I population, we have defined as patients with hepatocellular cancer, gastric cancer, renal cell cancer, and endometrial cell cancer, four different indications where both PD-1 blockade and VEGF blockade are effective. Our plan is to initiate that phase I study and get clinical data next year. We have stated publicly that there is tremendous interest, not only in this field, but in this asset.
What we do with this drug moving forward, we'll do what's best for our shareholders.
Perfect. I think we're about out of time. Really appreciate you coming to Piper Sandler Healthcare Conference and sharing insights on the story.
Thanks, Biren. Thanks so much for having us.
Good morning, everyone. Welcome to day one of our Piper Sandler Healthcare Conference. My name is Yasmeen Rahimi. I'm a Biotech Analyst here at Piper Sandler. Really thrilled to have the team from REGENX here. 2026 is a big year for REGENX. You guys have been the pioneers in gene therapy. Would love to kind of start off the role that sort of your views into 2026 and how you're thinking about some of the key inflection points, and then we'll go through each program one by one.
Sure. Yeah. It's a really big year for us in terms of we have really solid dates in mind for some really key milestones. The first is first quarter, February PDUFA date for our Hunter program. I've been with that program for nine years now, so it's exciting to see it getting to this point of review. We've had good success over the summer with the inspections. Next on the list is in early Q2, we've guided to top-line data for our Duchenne program. We completed enrollment last October and look forward to the results there. I can talk about more in depth on that. In September this year, we announced completion of enrollment. I think they're the largest gene therapy trials ever conducted with AbbVie. We are now pointing to top-line data for the subretinal program for wet AMD late next year.
Wonderful.
Lots to look forward to.
Lots to look for, lots of rich catalysts that are upcoming. You guys have made a tremendous amount of investment and work and hard work went into building a manufacturing facility. Help us understand sort of the capabilities that the facility has as one of the leaders in the gene therapy space.
Sure. Yeah. We started probably around 10 years ago when I joined building up the CMC approach. I think historically, FDA and others have been pretty critical of gene therapy manufacturing, saying it needed to be modernized. That is exactly what we set out to do. If you walk into our manufacturing facility located in Rockville, it will look like a biologics plant, suspension bioreactor with HEK293 cell line that we use. We have really sort of cracked the code on gene therapy expression levels for vector. We have published some of that at ASGCT. I think importantly, having control of manufacturing, particularly for the Duchenne program, which has a really high vector requirement, is a huge asset to us, a differentiator.
Wonderful. Maybe let's talk about our RGX-121, which is upcoming here with PDUFA date in February. I think recently you noted that the inspections have been completed. PDUFA date is on track. Just kind of help us understand sort of what is left to do between now and PDUFA and what your disclosures are going to look like between now and then.
Yeah. We'll certainly give a disclosure around February when the PDUFA date comes. The BLA was submitted as a rolling BLA. We submitted non-clinical, then CMC, and then the clinical module last. As you could expect, most of the review at this point is down to the clinical module. We published data in September with full 12-month data on all of the patients in the pivotal, which looked really exciting. Yeah, we're looking forward to proceeding to a PDUFA date, hopefully a positive decision. I think the manufacturing plays into that as well. The facility was inspected as part of that in the summer, and we got out of that with no observations, which is pretty rare. We feel like we've de-risked one key aspect of the gene therapy world in terms of CMC and non-clinical, looking really positive.
Maybe it would be also great to think about sort of how you're envisioning commercialization and be transitioned to become a commercial company with manufacturing and scalability on hand, which will be maybe a question that comes up is like finding patients, warehousing them, what work has been done, hires in terms of building the commercial team.
Yeah. We signed a deal early this year with NS Pharma. We are in a partnership in which NS Pharma will handle the commercialization aspect. We felt it's a bit too early for us to build out a sales team for an ultra-rare indication. The benefit we have is we do control the manufacturing supply chain. We'll have a lot of input, obviously, into the commercialization because many of the sites we're going to will be the same as what we used in the clinic as well. MPS is ultra-rare disease, and finding patients is actually pretty straightforward. There's emerging, I think I heard 40% of the states in the next year and a half will be doing newborn screening. That will be an automatic funnel to find patients. They're very aware of our program.
We've had a 10-year relationship with the MPS Society that will help us greatly with that. We are looking forward to it. I think we have all the elements for a successful launch.
How do you think 121 will play into the market?
I think one-time gene therapy is really, truly differentiating. If you think about the burden of care, which currently there aren't any treatments available for the CNS manifestation, for things like enzyme replacement therapy, patients have to come in many times weekly for infusions. Imagine the burden of having a child. A one-time gene therapy, I think, will be a very powerful alternative for patients. We expect really strong adoption.
Wonderful. As many investors are also aware, first of all, you will be the first gene therapy to enter the ERT market, which would be another key milestone for the space. Investors who follow the program understand that DNL310 also has an upcoming PDUFA date on April 26th. Maybe help us understand sort of the evolving landscape when it comes to the space with multiple gene therapy programs available and the differentiations of them.
Sure. Yeah. I just talked to a couple of people within patient advocacy groups. It's been 20 years since they've had anything new approved. Having two programs potentially approved is great for patients. Again, I like our position in the sense of a one-time gene therapy. I think our data, particularly we have data in younger patients. I think in terms of who are the right patients to dose and coming off newborn screening, once the damage is done, it can't be undone. Early treatment is going to be important. I think the strength of our data is in that younger patient population.
Great. Team, would love to talk about 202 and DMD. Maybe start off with helping us understand what is the strategic interest in 202 for DMD.
Yeah. I think it plays on a lot of strengths within the company. Number one, it's in rare disease, which we just talked about the Hunter program. That's a key element of our portfolio. Number two, our Chief Science Officer, Olivier Danos, has been working in Duchenne for 25 years or so. He had a lot of input, obviously, and drove the design of the construct, which includes the C-terminus. If you go all the way back to the 11S adcom, you'll see FDA reviewers talking about the value of making microdystrophin more like natural dystrophin. That automatically includes, if you do that, the C-terminus, which we were able to accomplish. What that does is it helps with restoring function once the muscle has been damaged through exercise. That gave us promise of delivering better functional benefit.
I think the last piece of the puzzle, well, maybe there's two more, but one is the immune suppression regimen that we're using. So far, we've had no SAEs in our phase I/II study. We'll be happy to roll out our safety update in Q2 top-line data. We feel very positive about that. Then playing into that is the manufacturing process. We're at 80% full capsid. So the majority of the product is the intended product. That's what allows us to maximize the dose and give the best possibility for functional benefit.
How do you think it differentiates versus other gene therapy programs in DMD?
I think that if we look at our phase one two data and we look at the benefit to risk profile, I think we have the best product in development. I say that because we're seeing improvement in patients that are seven and older, where automatically those patients are normally in a decline phase of their disease. We're seeing those children improving in function, not just stabilized. We're also, as I mentioned, not seeing safety events. Put the two together, I think we have a compelling case.
The data is on track for 2Q of next year. Maybe just housekeeping items. What type of data will you have on hand at the time of the disclosure? What is sort of the bar for success or the expectation going into the readout?
Yeah. We'll have in Q2, we'll have for all 30 patients, overall safety update. We'll also have data around the primary endpoint, which is microdystrophin, the proportion of patients at 10% and above for microdystrophin. We'll also have functional data, I would say on roughly 1/3 of those patients. It depends on visits and timing, etc. Key is at 12 months. We don't believe data earlier than that because it could be subject to immune suppression.